Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: ZNFX1

Green List (high evidence)

Green List (high evidence)

15 individuals from 8 families reported with multi-system inflammation and susceptibility to viral infections.

In addition, four indviduals from two unrelated kindreds reported with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis.

Created: 10 May 2021, 10:33 a.m. | Last Modified: 10 May 2021, 10:33 a.m.

Panel Version: 2.421

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Multisystem inflammation; susceptibility to viral infections

Publications

• 33872655
• 33876776

Green List (high evidence)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 10:59 a.m. | Last Modified: 8 Mar 2022, 10:59 a.m.

Panel Version: 2.532

Comment on list classification: New gene added by Boaz Palterer. Sufficient number of unrelated cases (10 - PMIDs: 33876776; 33872655) with immunopathology and biallelic variants in this gene to rate as Green at the next GMS panel update.

Created: 27 Apr 2021, 10:43 a.m. | Last Modified: 27 Apr 2021, 10:43 a.m.

Panel Version: 2.416

- Voyer et al. 2021 (PMID: 33876776) - Three patients from two unrelated kindreds with intermittent monocytosis and mycobacterial disease, including bacillus Calmette–Guérin-osis and disseminated tuberculosis, and without any known inborn error of IFN-γ. Both families were homozygous for different pLoF ZNFX1 variants (c.2876C>G, p.S959* and c.4815_4818del, p.E1606Rfs*10, respectively).

- Vavassori et al. 2021 (PMID: 33872655) - 13 patients from 8 families with immunodeficiency characterised by severe viral infections and systemic inflammatory disease, associated with biallelic variants in the ZNFX1 gene. Studies using patient-derived primary cells showed deregulated expression of interferon-stimulated genes and impaired clearance of virus infections by monocytes.

Created: 27 Apr 2021, 10:39 a.m. | Last Modified: 27 Apr 2021, 10:39 a.m.

Panel Version: 2.414

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 33876776
• 33872655

Green List (high evidence)

Multisystem Inflammation and Susceptibility to Viral infections in Human ZNFX1 Deficiency
15 patients from 8 families with an autosomal recessive immunodeficiency characterized by severe infections by both RNA and DNA viruses and virally triggered inflammatory episodes with hemophagocytic-lymphohistiocytosis-like disease, early-onset seizures, as well as renal and lung disease.
https://www.jacionline.org/article/S0091-6749(21)00613-8/fulltext

Created: 20 Apr 2021, 7:51 a.m. | Last Modified: 20 Apr 2021, 7:51 a.m.

Panel Version: 2.413

Le Voyer et al. described two patients from two unrelated kindreds with homozygous LOF variants in the ZNFX1 gene associated with mendelian susceptibility to mycobacterial disease (MSMD) and monocytosis. ( https://www.pnas.org/content/118/15/e2102804118 )
Sources: Literature

Created: 10 Apr 2021, 7:13 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Multisystem inflammatory disoder; viral infections; HLH